Standard recall schedule

• First invitation for screening at age 25 in England and Northern Ireland and age 20 in Wales and Scotland.
• Routine recall:
  • England: routine three-yearly recall between ages 25-49, then five-yearly recall until aged 65.
  • Scotland: routine three-yearly recall from age 20 until aged 60.
  • Wales: routine three-yearly recall from age 20 until aged 65.
  • Northern Ireland: routine three-yearly recall between ages 25-49, then five-yearly recall until aged 65.
• Consider offering a smear to patients above the upper age limit who have not been screened since age 50 or have had recent abnormal tests.

Interpreting smear results

Cells are analysed to look for abnormalities in the appearance of the nucleus and other aspects of cell morphology (dyskaryosis). There is some lack of standardisation among laboratories, but basically one can expect to see one of the following results on a report:

• Negative - endocervical cells with normal nuclei are seen.
• Inadequate - the average national rate for inadequate smears is about 9%. Inadequate smears may be caused by insufficient or unsuitable material on the smear, inadequate fixation, poor spreading of the material on the slide, the presence of pus, blood or inflammatory exudate, or excessive cytolysis (this may be due to drying out of the smear, or hormone therapy).
• Borderline - this is reported in approximately 5% of smears. Cells are seen with abnormal nuclei, but the pathologist cannot say for certain that they are indicative of dyskaryosis. Many patients revert to normal smears eventually. Human papillomavirus (HPV) infection is sometimes found in this group. Very few of these patients go on to develop cancer.
• Mild dyskaryosis - this occurs in approximately 5% of smears. Again, many women with this finding eventually revert to normal smears. HPV infection is a common association. Strictly speaking, the cervical intraepithelial neoplasia (CIN) grading system should not be used on smears but on cervical biopsy material obtained during colposcopy. However, mild dyskaryosis usually equates to CIN 1. Cancer is very unlikely.
• Moderate dyskaryosis - this usually equates to CIN 2 and is seen in approximately 1% of samples. CIN 2 is considered a precancerous condition with an intermediate probability of developing into cancer.
• Severe dyskaryosis - this usually equates to CIN 3. It occurs in about 0.5% of smears and is at the higher risk end of the cancer spectrum. About 0.1% of smears will show nuclear and other cellular changes suggestive of carcinoma, sometimes referred to as carcinoma in situ.
• Glandular neoplasia - occasionally, abnormalities of glandular cells are seen, suggestive of adenocarcinoma in situ, adenocarcinoma of the cervix, endometrial adenocarcinoma, or adenocarcinoma of an organ outside the uterus.

Management of results

Negative (normal)

It is appropriate to:

• Investigate and manage incidental findings. eg infections.
• Ensure that the patient is informed of the result.
• Recall as appropriate for a negative result.

Inadequate

• Repeat sample immediately after treating any infection or atrophy, preferably within three months.
• Repeat sample as soon as convenient if technically inadequate.
• If persistent (three inadequate samples), advise assessment by colposcopy.

Borderline

• Borderline nuclear change in endocervical cells - refer for colposcopy.
• Borderline nuclear change in squamous cells:
• Treat any associated condition and repeat the screen at no more than six months (particularly important where there is an association with HPV). The majority of smears will return to normal by this stage.
• Refer for colposcopy if there are three smears in a series (reported as borderline nuclear change in squamous cells) without the woman being returned to routine recall, or three borderline or more severe results in a 10-year period.
• Three consecutive negative results, six months apart, are required before returning to routine recall.
• Repeat a sample in three to six months when the differential diagnosis is between benign/reactive changes and higher degrees of dyskaryosis or possible glandular neoplasia.
• The laboratory may recommend a repeat screening in a shorter interval, or that gynaecological referral should be considered.

In some areas of the UK, women with borderline or mild dyskaryotic changes are offered an HPV DNA test. Women who test positive for high-risk types of HPV are referred for a colposcopy straight away. Research has shown that HPV DNA testing leads to earlier detection of clinically relevant CIN grade 2 or worse, which when adequately treated, improves protection against CIN grade 3 or worse and cervical cancer.^[3] High-risk HPV types (16, 18, 31, 33) have been found to be present in close to 100% of all cervical cancers. Equally, women with a mild or borderline smear result, who have no evidence of high-risk HPV infection are very unlikely to develop cervical cancer.^[4] HPV testing is not currently recommended for primary screening, but this may change.^[5][6]

Mild dyskaryosis

• Ideally, women should be referred for colposcopy after one mild dyskaryotic smear, but it remains acceptable to recommend a repeat test within six months - many will have returned to normal by this stage.
• Always refer for colposcopy after two tests reported as mild dyskaryosis without a return to routine recall.
• Three consecutive negative results, six months apart, are required before returning to routine recall.
• If a single mild dyskaryotic result is obtained after treatment for carcinoma in situ stage 2 or worse, refer for colposcopy.
• If, in a 10-year period, there are three borderline or more severe results, refer to colposcopy.

Moderate dyskaryosis

Refer for colposcopy.

Severe dyskaryosis

Refer for colposcopy.

Other results

• Inflammatory changes usually indicate infection:^[7]
  • Mild inflammation
  • Moderate inflammation
  • Severe inflammation
• Actinomyces: a smear may show actinomyces-like organisms (ALOs), especially if an intrauterine contraceptive device (IUCD) is in situ; however, unless there is clinical evidence of pelvic inflammatory disease, they are of no significance.
• Candida: many treatments are available including topical or oral imidazoles.
• Gardnerella: treatment is metronidazole 400-500 mg twice daily for seven days.
• Herpes: antiviral therapy is effective in both initial attacks and recurrences. The licensed drugs are aciclovir, valaciclovir and famciclovir. Oral therapy is required. Topical treatment is inadequate. There is no benefit in combining topical and oral therapy.
• Koilocytosis: this is the presence of koilocytes (cells infected by HPV). They typically have shrivelled nuclei with a halo.^[8] They have a low prognostic value for CIN.^[9]
• Trichomonas: metronidazole is the treatment of choice.
• Viral inflammation unspecified.